Impact of age on acute post-TBI neuropathology in mice expressing humanized tau: a Chronic Effects of Neurotrauma Consortium Study

Mouzon, B. et al. (2018) Impact of age on acute post-TBI neuropathology in mice expressing humanized tau: a Chronic Effects of Neurotrauma Consortium Study. Brain Injury, 32(10), pp. 1285-1294. (doi: 10.1080/02699052.2018.1486457) (PMID:29927671)

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Objectives: We hypothesized that polypathology is more severe in older than younger mice during the acute phase following repetitive mild traumatic brain injury (r-mTBI). Methods: Young and aged male and female mice transgenic for human tau (hTau) were exposed to r-mTBI or a sham procedure. Twenty-four hours post-last injury, mouse brain tissue was immunostained for alterations in astrogliosis, microgliosis, tau pathology, and axonal injury. Results: Quantitative analysis revealed a greater percent distribution of glial fibrillary acid protein and Iba-1 reactivity in the brains of all mice exposed to r-mTBI compared to sham controls. However, no noticeable difference was observed between the young and aged groups as initially hypothesized. With respect to axonal injury, the number of amyloid precursor protein-positive profiles was increased in young vs aged mice post r-mTBI. An increase in tau immunoreactivity was found in young and aged injured male hTau mice. Conclusions: We report the first evidence in our model that r-mTBI precipitates a complex sequelae of events in aged vs young hTau mice at an acute time point, typified by an increase in phosphorylated tau and astroglisosis, and a diminished microgliosis response and axonal injury. These findings suggest differential age-dependent effects in TBI pathobiology.

Item Type:Articles
Additional Information:This work was supported by grant funding from: Department of Defense, Chronic Effects of Neurotrauma Consortium (CENC) Award W81XWH-13-2-0095 and Department of Veterans Affairs CENC Award I01 CX001135. Dr. Stewart is supported by NIH grants R01NS038104 & R01NS094, Department of Defense, and an NHS Research Scotland Career Researcher Fellowship.
Glasgow Author(s) Enlighten ID:Stewart, Dr William
Authors: Mouzon, B., Saltiel, N., Ferguson, S., Ojo, J., Lungmus, C., Lynch, C., Algamal, M., Morin, A., Carper, B., Bieler, G., Mufson, E. J., Stewart, W., Mullan, M., and Crawford, F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:Brain Injury
Publisher:Taylor & Francis
ISSN (Online):1362-301X
Published Online:21 June 2018
Copyright Holders:Copyright © 2018 Taylor & Francis Group, LLC
First Published:First published in Brain Injury 32(10): 1285-1294
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
696421Characterising amyloid pathologies after traumatic brain injuryWilliam StewartNational Institute of Health (NIH-BETH)2R01NS038104-15A1RI NEUROSCIENCE & PSYCHOLOGY
695641Longitudinal Assessment of Brain Structure and Function in Myotonic DystrophyDarren MoncktonNational Institutes of Health (NIH)R01NS094387RI MOLECULAR CELL & SYSTEMS BIOLOGY